Potential impact on mental health in patients with treatment-resistant schizophrenia - clozapine augmentation with long-acting parenteral antipsychotics: a case series.

INTRODUCTION: The rate of pharmacoresistance among in patients diagnosed with schizophrenia is around 30%. Clozapineis the drug of choice for these patients; however, an adequate response to treatment doesn't always occur. One of the possible augmentation approaches, specifically for non-adherent patients, is the administration of long-acting parenteral antipsychotics. Our goal was to evaluate previous experiences of administering a combination of the atypical antipsychotic clozapine and long-acting injectable antipsychotics to pharmacoresistant patients at the Department of Psychiatry the Czech Republic and to assess the safety and effectiveness of such administration. METHODS: A retrospective evaluation of patient case studies was conducted for those who were hospitalized in the Ward for the therapy of Psychotic disorders between 2016 and 2020 and had a medication history of combining clozapine and depot antipsychotics. RESULTS: Over half of the patients had no illness relapses during the observed period. The clinical manifestation of adverse effects from combination therapy appears low in our patient sample, primarily involving mild and pharmacologically manageable side effects (tachycardia). Only one of the cases recorded neutropenia, which led to discontinuation of clozapine; the patient was maintained on long-acting injectable antipsychotics medication. CONCLUSION: From our findings, it can be inferred that augmenting clozapine with depot antipsychotics is a potential therapeutic intervention that pharmacoresistant patients could benefit from. However, it is essential to emphasize that this therapeutic approach should only be administered after carefully considering the patient's existing treatment. It should be strictly individualized based on the treating physician's or clinical pharmacist's sufficient professional experience.

Dietary risk factors for inflammatory bowel diseases in a high-risk population: Results from the Faroese IBD study.

Background: The Faroe Islands currently have the highest recorded inflammatory bowel disease (IBD) incidence in the world. Objective: This study investigated environmental risk factors for IBD in the Faroese population. Methods: Environmental exposure data including lifestyle risk factors and neurotoxicants collected for over 30 years were retrieved from the Children's Health and the Environment in the Faroes (CHEF) cohorts including mainly mother-child pairs, with exposure data collected from pregnant mothers. For lifestyle risk factors, the incidence of IBD and ulcerative colitis (UC) was calculated as the rate ratio (RR) with 95% confidence intervals (CI) in exposed versus non-exposed persons. For neurotoxicants RR was calculated for persons with high versus low exposure. Results: Six cohorts included 5698 persons with complete follow-up data and at least one exposure, and 37 were diagnosed with IBD. For pilot whale/blubber, the RR was 1.02 (95% CI, 0.48-2.18); RR of 1.01 for fish (95% CI, 0.35-2.91); and of the pollutants studied, a statistical significantly increased risk was found for 1,1,1,-trichloro-2,2-bis-(p-chlorophenyl) ethane (p,p'-DDT); RR 3.04 (95% CI, 1.12-8.30). RRs were 1.96 (95% CI, 1.03-3.73) for smoking and 1.10 (95% CI, 0.55-2.19) for alcohol intake. Conclusion: The high IBD incidence is unlikely to be caused by special dietary habits or by environmental pollutants.

[Pediatric acute dacryocystitis due to frontoethmoidal mucocele]. / Akute Dakryozystitis im Kindesalter bei frontoethmoidaler Mukozele.

BACKGROUND: Pediatric acute dacryocystitis typically develops due to persistence of Hasner's membrane. Pediatric paranasal mucoceles are rare entities. In contrast, chronic dacryocystitis in cases of congenital dacryostenosis is one of the most frequent pediatric ophthalmologic issues. METHODS: The case report of a 10-year-old girl suffering acute dacryocystitis is presented. RESULTS: The area around the left lacrimal sac showed a painful swelling with edema and hyperemia. Systemic and local antibiotic therapy resulted in only slight improvement. Dacryoendoscopy detected acute dacryocystitis with significant stenosis of the nasolacrimal duct. The nasolacrimal duct was widened dacryoendoscopically and autostable bicanalicular nasolacrimal intubation was performed. Nevertheless, the lacrimal ducts were blocked subtotally and a widening of the ethmoid on the left side was shown by rhinoscopy. Magnetic resonance imaging confirmed a frontoethmoidal mucocele which was treated by marsupialization. During the 24-month follow-up there was no recurrence of acute dacryocystitis. There were no signs of sinusitis. CONCLUSION: Paranasal mucoceles, e. g., ethmoidal mucoceles, can compress the lacrimal pathways and cause acute lacrimal inflammation in childhood. Paranasal mucoceles should thus be excluded in cases of unclear masses in the lacrimal region.

[Dacryoliths and Iatrogenic Foreign Bodies as Classical Triggers for Inflammatory Pseudotumors of the Lacrimal Drainage System]. / Dakryolithen und iatrogene Fremdkörper als klassische Auslöser entzündlicher Pseudotumoren der ableitenden Tränenwege.

BACKGROUND: Tumors of the lacrimal duct are rare. Inflammatory pseudotumors do not represent neoplasias as such. Chronic inflammation may lead to an angiomatous granulation tissue. PATIENTS: The first case presents a 53-year-old male patient suffering a mass of the mediocaudal orbit after an acute dacryocystitis has been cured. Using diagnostic dacryoendoscopy, a large dacryolith was detected. Removing the concrement, via external dacryocystorhinostomy, a polypous tissue appeared which was resected as well. The second case concerns a 29-year-old female patient. She had a lacrimal surgery with stenting seven years prior to surgery. The patient's history revealed recurrent mucous secretion of the tear duct and tenderness of the lacrimal sac. An intrasaccal silicon foreign body could be confirmed by dacryoendoscopy. An external dacryocystorhinostomy was performed and the material was extracted. Hereby, an inflammatory tissue mass filling the whole efferent tear duct was removed. RESULTS: In both patients, external dacryocystorhinostomy was performed complication-free. Surgery enabled the reconstruction of the nasolacrimal duct. Temporary autostable silicon intubation was inserted into the nasolacrimal duct (case 1 and 2), as well into osteotomy (case 2). Histologically, reactive granulation tissue was confirmed. During the follow-up of 9 months (patient 1) and 12 months (patient 2), patients were free of complaints. Lacrimal stentings were removed uneventfully and completely. CONCLUSIONS: Dacryoliths and intrasaccal foreign bodies may cause a chronic dacryocystitis. Due to inflammation, reactive tissue proliferation can be initiated. In these cases, a hypertrophic granulation arose. Endogenous (dacryoliths) and exogenous (iatrogenic foreign bodies) triggers may be underlying reasons. Histological examination is essential for differentiating other inflammatory pathologies or tumors.

[Comparison of trabeculectomy and canaloplasty : Pressure reducing effect and postoperative interventions/complications]. / Vergleich von Trabekulektomie und Kanaloplastik : Drucksenkender Effekt und postoperatives Komplikations- und Interventionsspektrum.

BACKGROUND: Trabeculectomy (TET) is still the most commonly performed surgical treatment in dealing with primary open angle glaucoma (POAG) worldwide. Canaloplasty (CP) as a nonpenetrating surgical procedure has recently become a new option to efficiently reduce intraocular pressure (IOP). OBJECTIVES: This study compared both surgical procedures concerning the efficacy in IOP reduction. Furthermore we compared IOP fluctuation, postoperative medication, visual acuity, astigmatism and postoperative interventions and complications. MATERIALS AND METHODS: Retrospectively studied were 32 eyes after canaloplasty and 31 eyes after trabeculectomy. IOP, IOP fluctuation range, visual acuity, astigmatism and glaucoma medication were recorded preoperatively and after a follow-up of 6 and 12 months. In addition we compared postoperative complications and interventions of both surgical procedures. RESULTS: The mean IOP after canaloplasty was significantly reduced from 16.0 ± 3.5 mm Hg to 12.5 ± 3.3 mm Hg. Trabeculectomy also achieved a significant IOP reduction from 15.3 ± 3.5 mm Hg to 11.0 ± 2.6 mm Hg. Comparing the two surgical procedures there was no evidence for a significant difference in IOP reduction. Trabeculectomy was able to reduce the number of postoperative glaucoma medication substances better than canaloplasty. There was no difference in postoperative visual acuity or astigmatism. Concerning postoperative complications and interventions canaloplasty treatment was associated with a less severe spectrum of complications. CONCLUSION: Both procedures provide a safe and efficient IOP reduction. Trabeculectomy is able to achieve an even better IOP reduction without application of additional postoperative medication. Canaloplasty requires shorter inpatient stay, less frequent postoperative checkups and interventions as well as a less severe spectrum of complications.

[Scanning electron microscopic investigations of cutting edge quality in lamellar keratotomy using the Wavelight femtosecond laser (FS-200) : What influence do spot distance and an additional tunnel have?] / Rasterelektronenmikroskopische Untersuchungen der Schnittqualität lamellärer Keratotomien nach Anwendung des Wavelight-Femtosekundenlasers (FS-200) : Welchen Einfluss haben Spotabstand und zusätzlicher Tunnel?

BACKGROUND: Femtosecond lasers (fs-lasers) are established cutting instruments for the creation of LASIK flaps. Previous studies often showed even rougher surfaces after application of fs-laser systems compared to lamellar keratotomy with mechanical microkeratomes. When cutting the cornea with fs-lasers, an intrastromal gas development occurs, which has a potentially negative influence on the cutting quality if the gas cannot be dissipated; therefore, manufacturers have chosen the way of gas assimilation in so-called pockets. The investigated system creates a tunnel which opens under the conjunctiva. The aim of this study was to investigate the effects of a tunnel as well as the influence of different spot distances on the quality of cut surfaces and edges. MATERIAL AND METHODS: In this experimental study on freshly enucleated porcine eyes (n = 15), the following cuts were carried out with the FS-200 (Wavelight, Erlangen, Germany): 1. standard setting (spot and line separation 8 µm), 2. with tunnel for gas drainage, 3. without gas-conducting tunnel, 4. with increased spot spacing (spot and line separation 9 µm instead of 8 µm) and 5. with reduced spot spacing (spot and line separation 7 µm instead of 8 µm). Subsequently, scanning electron microscopy (FEI Quanta 650, Hillsboro, OR) of the cut edges and surfaces as well as the gas drain tunnel were performed. The evaluation was based on an established score. RESULTS: The current fs-laser system (200 Hz) is able to create smooth cutting surfaces and sharp edges. The changed density of laser pulses compared to the standard settings with a reduced or increased distance between the pulses, did not achieve any further improvement in the surface quality. The gas-conducting tunnel could be detected by scanning electron microscope. In the case of cutting without a tunnel, roughened surfaces and irregularities on the cutting edges were found. CONCLUSION: When the FS-200 fs-laser is used, LASIK cuts with very smooth cut surfaces and sharp cutting edges are achieved. This is only valid as long as an additional tunnel with the fs-laser is placed under the conjunctiva. It can be assumed that the resulting gas is effectively drained through this tunnel. The installation of the tunnel represents a new possibility to replace previous techniques of gas assimilation in deeper lying cutting areas.

Severity-dependent differences in early management of thoracic trauma in severely injured patients - Analysis based on the TraumaRegister DGU®.

BACKGROUND: Major trauma is associated with chest injuries in nearly 50% of multiple injuries. Thoracic trauma is a relevant source of comorbidity throughout the period of multiply-injured patient care and may require swift and well-thought-out interventions in order to avert a deleterious outcome. In this epidemiological study we seek to characterize groups of different thoracic trauma severity in severely injured patients and identify related differences in prehospital and early clinical management. This may help to anticipate necessary treatment for chest injuries. METHODS: Patients documented between 2002 and 2012 in the TraumaRegister DGU®, aged ≥ 16 years, determined Injury Severity Score ≥ 16, and documentation from European trauma centers were analyzed. Isolated brain injury and severe head injury (Abbreviated Injury ScaleHead ≥ 4) led to patient exclusion. Patient subgroups were formed according to the Abbreviated Injury ScaleThorax as Controls, AIS-2, AIS-3, AIS-4, and AIS-5/6. Demographic and clinical characteristics comparing the aforementioned groups were evaluated using descriptive statistics. RESULTS: Twenty two thousand five hundred sixty five predominantly male (74%) patients, mean age 45.7 years (SD 19.3), suffering from blunt trauma (95%), and presenting a mean Injury Severity Score of 25.6 (SD 9.6) were analyzed. Higher thoracic injury severity was associated with more different thoracic injuries. The highest rate of prehospital intubation (58%) occurred in AISThorax-5/6. The worse the chest trauma, the more chest tubes were placed prehospitally, peaking at 22% in AISThorax-5/6. Out-of-hospital cardiopulmonary resuscitation was successfully performed in 11% in AISThorax-5/6 compared to 1%-3% in lesser thoracic trauma severity. Massive transfusion and emergency surgery was highest in AISThorax-5/6 compared to lesser thoracic injury (12% vs. 5%-7% and 17% vs. 3%-7%) and both were independently associated with thoracic injuries in patients with AISThorax ≥ 4. CONCLUSIONS: We provide epidemiological data on trauma mechanism, concomitant injuries, frequencies of emergency interventions and outcome associated with different thoracic trauma severity. Prehospital and early clinical management is more complex when AISThorax is ≥ 4. Severely injured patients with critical thoracic trauma are most challenging to take care of with highest rates in prehospital intubation, cardiopulmonary resuscitation, chest tube placements, blood transfusions as well as emergency surgery.

Inflammatory bowel diseases in Faroese-born Danish residents and their offspring: further evidence of the dominant role of environmental factors in IBD development.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is record high in the Faroe Islands, and many Faroese emigrate to Denmark, where the IBD incidence is considerably lower. AIM: To study the IBD incidence in first-, second- and third-generation immigrants from the Faroe Islands to Denmark to assess the extent to which the immigrants adopt the lower IBD incidence of their new home country. METHODS: Data on Faroese-born Danish residents and their children were retrieved from the Danish Central Population Register for 1980-2014. Incident IBD cases were identified from the Danish National Patient Register. Standardised Incidence Ratios (SIRs) were used to compare the IBD risk in immigrants with that of Danes. 95% confidence intervals (CI) were calculated using the square-root transform. RESULTS: First-generation Faroese immigrants had a higher IBD incidence than Danes, SIR 1.25 (95% CI, 0.97-1.59) for men and 1.28 (95% CI, 1.05-1.53) for women. This excess risk derived from ulcerative colitis (UC), SIR 1.44 (95% CI, 1.10-1.87) for men and 1.36 (95% CI, 1.09-1.68) for women. No excess risk was found for Crohn's disease (CD). The UC risk was nearly doubled during the immigrants' first 10 years in Denmark; SIR 2.13 (95% CI, 1.52-2.92) for men and 1.63 (95% CI, 1.19-2.18) for women. CONCLUSIONS: Although some impact of genetic dilution cannot be excluded, our findings indicate importance of gene-environment interplay in UC, as the excess UC risk in Faroese immigrants to Denmark disappeared over time and over one generation in men and over two generations in women.

Non-Union in Upper Limb Fractures - Clinical Evaluation and Treatment Options.

Although non-unions in the upper limb are rare different treatment options of this challenging situation are still affected with up to 20% of failure rate due to current literature. Risk factors for delayed and non-union of fractures are mainly the size of the fracture gap and bone loss of open fractures or in primary surgery followed by other relevant internal and external factors. In the upper limb non-unions of long bones are described with up to 30% after operative intervention. Especially in the upper limb range of motion is limited in non-union cases and disables adjacent joints like the shoulder, elbow and wrist hence reducing the total activity level of affected patients. Beside careful investigation of the causes leading to the non-union a comprehensive treatment plan should be defined to achieve successful results. Treatment can be non-operative in several, selected cases, but in the majority of cases revision surgery is necessary to achieve osseous healing. Our own experience showed that non-union in the upper limb are rare and account for only 1.7% of all surgical managed upper limb fractures. Non-union of upper limb fractures occur most frequently in clavicle fractures followed by humeral fractures. Atrophic non-union is the most frequent reason for osseous non-union (57%) and osseous healing after revision surgery in non-unions is completed after a mean of 6.45 months. This article will give a brief overview of the genesis, clinical evaluation, treatment options and recommendations in upper limb non-unions according to the current literature. Key words: fracture, upper-limb, non-union, osteosynthesis, cancellous bone-graft.

Comminuted Fracture of Elbow - Ostheosynthesis vs. Total Joint Replacement.

Comminuted fractures of the elbow are very rare and in most cases very complex and the successful treatment can be a challenge for the treating surgeon. Due to the elbow joint's complex functional anatomy, the multi-fragmentary nature of many fractures and concomitant destabilizing associated injuries, comminuted fractures of the elbow still present a serious challenge for the orthopedic surgeon. Especially in more severe communicated injuries an osteosynthesis or endoprosthesis must be discussed with the patient. There is a lack of clear treatment recommendations based on solid evidence. An overview of the literature including a treatment algorithm to guide decision making for the distal humeral fracture in the adults is presented and own results are analyzed. Key words: comminuted fracture of elbow, total joint replacement of the elbow, elbow prosthesis, elbow arthroplasty, distal humeral fracture.

Outcome and predictors for successful resuscitation in the emergency room of adult patients in traumatic cardiorespiratory arrest.

BACKGROUND: Data of the TraumaRegister DGU® were analyzed to derive survival rates, neurological outcome and prognostic factors of patients who had suffered traumatic cardiac arrest in the early treatment phase. METHODS: The database of the TraumaRegister DGU® from 2002 to 2013 was analyzed. The main focus of this survey was on different time points of performed resuscitation. Descriptive and multivariate analyses (logistic regression) were performed with the neurological outcome (Glasgow Outcome Scale) and survival rate as the target variable. Patients were classified according to CPR in the prehospital phase and/or in the emergency room (ER). Patients without CA served as a control group. The database does not include patients who required prehospital CPR but did not achieve ROSC. RESULTS: A total of 3052 patients from a total of 38,499 cases had cardiac arrest during the early post-trauma phase and required CPR in the prehospital phase and/or in the ER. After only prehospital resuscitation (n = 944) survival rate was 31.7 %, and 14.7 % had a good/moderate outcome. If CPR was required in the ER only (n = 1197), survival rate was 25.6 %, with a good/moderate outcome in 19.2 % of cases. A total of 4.8 % in the group with preclinical and ER resuscitation survived, and just 2.7 % had a good or moderate outcome. Multivariate logistic regression analysis revealed the following prognostic factors for survival after traumatic cardiac arrest: prehospital CPR, shock, coagulopathy, thorax drainage, preclinical catecholamines, unconsciousness, and injury severity (Injury Severity Score). CONCLUSIONS: With the knowledge that prehospital resuscitated patients who not reached the hospital could not be included, CPR after severe trauma seems to yield a better outcome than most studies have reported, and appears to be more justified than the current guidelines would imply. Preclinical resuscitation is associated with a higher survival rate and better neurological outcome compared with resuscitation in the ER. If resuscitation in the ER is necessary after a preclinical performed resuscitation the survival rate is marginal, even though 56 % of these patients had a good and moderate outcome. The data we present may support algorithms for resuscitation in the future.

Electroencephalographic study showing that tactile stimulation by fabrics of different qualities elicit graded event-related potentials.

BACKGROUND/PURPOSE: Neurophysiologic data on reactions of the human brain towards tactile stimuli evoked by fabrics moved on the skin are scarce. Furthermore, evaluation of fabrics' pleasantness using questionnaires suffers subjective biases. That is why we used a 64-channel electroencephalography (EEG) to objectively evaluate real-time brain reactions to fabric-skin interactions. METHODS: Tactile stimuli were triggered by selected fabrics of different qualities, i.e. modal/polyamide single jersey, cotton double rib and a jute fabric, applied hidden to either the palm or forearm of 24 subjects via a custom-made fabric-to-skin applicator called SOFIA. One-way anova analysis was carried out to verify the EEG data. RESULTS: The modal/polyamide fabric applied to the forearm and palm led to slightly stronger emotional valence scores in the brain than the conventional or baseline fabric. Furthermore, the single jersey elicits significant higher event-related potential (ERP) signals in all subjects when applied to the forearm, suggesting less distraction and better cognitive resources during the fabric/skin interaction. The brain thus reacts with instantaneous ERP to tactile stimulation of fabrics and is able to discriminate different qualities via implicit preferences. CONCLUSION: The test procedure described here may be a tool to evaluate the fabric feel with the exclusion of subjective biases.

Radial head prosthesis after radial head and neck fractures - current literature and quality of evidence.

Due to the elbow joint's complex functional anatomy, the multifragmentary nature of many fractures and concomitant destabilizing associated injuries, dislocated fractures of the radial head and neck still present a serious challenge for the orthopedic surgeon. Thorough knowledge of the elbow's anatomy and biomechanics is essential to analyze and understand the injury and plan its treatment. The aim of a differentiated therapy approach is to restore the joint's anatomy and kinetics, stable and painless joint function, and to avoid or at least delay posttraumatic joint changes. The degree of dislocation, stability of fragments, size and number of fractured joint surfaces and associated bony and ligamentous injuries (and the instability they incur) must be addressed in the therapy regimen. There are various treatment options depending on the injury's classification, i.e. a Mason I fracture is treated conservatively, while more severe injuries may require osteosynthesis and endoprosthesis. There is a lack of clear therapy recommendations based on solid evidence regarding Mason classification types III-IV. In particular expert opinions diverge and study results are inconsistent. Especially the value of radial head arthroplasty is still hotly debated. Key words: radial head fracture, radial head prosthesis, radial neck fracture, Mason classification, radial head arthroplasty, elbow injury.

[The influence of VEGF inhibitors on corneal endothelium after injection into the anterior chamber in a porcine eye model]. / Einfluss von VEGF-Inhibitoren auf das Hornhautendothel bei Injektion in die Vorderkammer am Modell des Schweineauges.

BACKGROUND: The injection of antiangiogenic agents, such as ranibizumab (Lucentis®) and bevacizumab (Avastin®) into the anterior chamber of the eye represents a suitable alternative for treating neovascular glaucoma by reducing intraocular pressure. OBJECTIVES: As the antiangiogenic substances are in direct contact with the sensitive corneal endothelium, the aim of this study was to show the effects of intracameral injection of ranibizumab and bevacizumab on this cell layer. METHODS: Each injection consisted of 50 µl containing either ranibizumab (0.5 mg/0.05 ml), bevacizumab (1.25 mg/0.05 ml) or triamcinolone containing benzyl alcohol (2 mg/0.05 ml) which was used as the control group. These compounds were injected into the anterior chamber of pig eyes. Afterwards the corneas were dissected, fixed, examined by a scanning electron microscopy and evaluated according to a specified score. Assessment of the endothelium was carried out by evaluating the condition of microvilli, cell borders, cell surface and cell pattern. The findings were compared to untreated corneas and those injected with 50 µl of balanced salt solution (BSS). RESULTS: The corneal endothelium exposed to the antiangiogenic substances showed only minor changes in comparison to the controls treated only with BSS. Also seen during this research was the irreversible cell damage in the control group using triamcinolone. CONCLUSION: Ranibizumab and bevacizumab have no damaging effects on the corneal endothelium when used in the anterior chamber. They can be administered as an intracameral injection for the treatment of rubeotic secondary glaucoma. Triamcinolon containing benzyl alcohol causes severe damage to the endothelial cells of the cornea by direct contact.

A phase I schedule dependency study of the aurora kinase inhibitor MSC1992371A in combination with gemcitabine in patients with solid tumors.

INTRODUCTION: MSC1992371A is an aurora kinase inhibitor with potential antitumor activity. METHODS: This trial established the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of oral MSC1992371A given before or after gemcitabine (1,000 mg/m(2)) in a 21-day cycle in patients with advanced malignancies. In schedule 1 (n = 31), gemcitabine was administered on days 1 and 8 followed by escalating doses of MSC1992371A on days 2 and 9. In schedule 2 (n = 35), MSC1992371A was given on days 1 and 8 followed by gemcitabine on days 2 and 9. Patients had a range of solid tumors, the most frequent of which was colorectal (n = 19). RESULTS: In both schedules, the 37 mg/m(2) dose level was defined as the MTD. The main DLT was grade 4 neutropenia. Adverse events consisted of neutropenia, thrombocytopenia, asthenia, fatigue, nausea, vomiting, anorexia, and diarrhea. Administration of MSC1992371A prior to gemcitabine had no effect on the metabolism or elimination of gemcitabine. Time to reach maximum plasma concentration and area under the plasma concentration-time curve for MSC1992371A increased proportionally with dose. Exploration of drug-target-related and tumor biomarkers did not identify predictors of biologic activity or response. Two patients (1 with lung carcinoma and 1 with hepatocellular carcinoma) had durable partial responses in schedule 2, and 5 patients had stable disease (SD) lasting 6 - 14 months. CONCLUSION: Oral MSC1992371A can be administered at a MTD of 37 mg/m(2) in combination with the standard 1,000 mg/m(2) dose of gemcitabine, but hematologic toxicity requires careful monitoring. Preliminary signs of efficacy were indicated by durable responses and SD.

[Does simulator-based team training improve patient safety?]. / Verbessern simulatorbasierte Teamtrainings die Patientensicherheit?

Patient safety became paramount in medicine as well as in emergency medicine after it was recognized that preventable, adverse events significantly contributed to morbidity and mortality during hospital stay. The underlying errors cannot usually be explained by medical technical inadequacies only but are more due to difficulties in the transition of theoretical knowledge into tasks under the conditions of clinical reality. Crew Resource Management and Human Factors which determine safety and efficiency of humans in complex situations are suitable to control such sources of error. Simulation significantly improved safety in high reliability organizations, such as the aerospace industry.Thus, simulator-based team training has also been proposed for medical areas. As such training is consuming in cost, time and human resources, the question of the cost-benefit ratio obviously arises. This review outlines the effects of simulator-based team training on patient safety. Such course formats are not only capable of creating awareness and improvements in safety culture but also improve technical team performance and emphasize team performance as a clinical competence. A few studies even indicated improvement of patient-centered outcome, such as a reduced rate of adverse events but further studies are required in this respect. In summary, simulator-based team training should be accepted as a suitable strategy to improve patient safety.

[German trauma centers: level-dependent differences in polytrauma care regarding resources and diagnostic concepts]. / Polytraumaversorgung in Deutschland: Klinikabhängige Unterschiede in der Ressourcenvorhaltung und bei diagnostischen Konzepten.

BACKGROUND: The aim was to survey the radiological diagnostics and type of primary radiological examination of polytraumatized patients treated in German hospitals at various levels in the three-tiered system. MATERIAL AND METHODS: A questionnaire was sent in October 2007 to every traumatology department registered in the DGU (German Society for Trauma Surgery) databank and forms returned by January 2008 were included in this study. RESULTS: A total of 273 (54.71 %) of forms were returned and were applicable to statistical analysis. In the three-tiered hospital system 35.9 % of returned questionnaires came from third-tier hospitals, 41.02 % from second-tier and 23.08 % from highest tier (maximum care) hospitals. With a higher hospital level of inpatient care more computed tomography (CT) scans were examined by a radiologist during 24 h daily (p = 0.0014) and CT scanners were located closer to the resuscitation room (p < 0.0001). We found significant differences in the ratios of primary whole-body CTs (WBCT) performed depending on the hospital level: third-tier hospitals 44 %, second tier hospitals 67 % and maximum care hospitals 84 % (p < 0.05). CONCLUSIONS: Standardized structures regarding radiological diagnostics of polytraumatized patients do not exist at either the same level of the three-tiered hospital system or between levels of care of German hospitals..

Phase I study of pulsatile 3-day administration of afatinib (BIBW 2992) in combination with docetaxel in advanced solid tumors.

BACKGROUND: A phase I study to assess the maximum tolerated dose (MTD) of a short course of afatinib in combination with docetaxel for the treatment of solid tumors. METHODS: Patients with advanced solid malignancies received docetaxel 75 mg/m(2) intravenously on day 1 and oral afatinib once daily on days 2-4, in 3-week treatment cycles. The afatinib dose was escalated in successive cohorts of 3-6 patients until dose-limiting toxicity (DLT). The MTD cohort was expanded to 13 patients. Pharmacokinetic parameters were assessed. RESULTS: Forty patients were treated. Afatinib doses were escalated to 160 mg/day in combination with 75 mg/m(2) docetaxel. Three patients had drug-related DLTs during cycle 1. The MTD was defined as 90 mg/day afatinib (days 2-4) with docetaxel 75 mg/m(2). The most frequent drug-related adverse events (all grades) were alopecia, diarrhea, stomatitis (all 50 %) and rash (40 %, all grade ≤ 2). Three patients had confirmed responses, two patients had unconfirmed responses and nine patients had durable stable disease >6 cycles. No pharmacokinetic interaction was observed. CONCLUSION: Afatinib 90 mg administered for 3 days after docetaxel 75 mg/m(2) is the MTD for this treatment schedule and the recommended phase II/phase III dose. This combination showed anti-tumor activity in phase I, with a manageable adverse-event profile.